Cigarette smoke extract induces thymic stromal lymphopoietin expression, leading to T(H)2-type immune responses and airway inflammation.
BACKGROUND
Both active and passive smoking are considered to be risk factors for asthma development. However, the precise mechanisms involved remain elusive. Recently, thymic stromal lymphopoietin (TSLP) has been shown to play a key role in the development of T(H)2-type allergic inflammation in patients with asthma.


OBJECTIVE
The aim of this study was to investigate whether there was a causal relationship between cigarette smoke exposure and TSLP expression in the lung.


METHODS
We examined the effects of repeated intranasal exposure of cigarette smoke extract (CSE) on TSLP mRNA and protein expression in the mouse lung by means of real-time PCR, Western blotting, and immunohistochemistry. We also examined the effects of intranasal exposure of CSE plus ovalbumin (OVA) on T(H)2-type immune responses and lung pathology.


RESULTS
Repeated exposure of CSE induced TSLP mRNA and protein expression, which was inhibited by treatment with antioxidative N-acetylcysteine and by TNF-alpha receptor I deficiency. In addition, the intranasal exposure of CSE simultaneously with OVA induced OVA-specific T(H)2-type immune responses and airway inflammation, which were inhibited by the blockade of the TSLP activity.


CONCLUSIONS
CSE induced TSLP expression in the mouse lung in an oxidative stress-dependent and TNF-alpha receptor I-dependent manner, and when challenged simultaneously with an antigen, CSE promoted the development of airway inflammation in association with T(H)2-type immune responses.
Nakamura
Yuki
Y
Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Miyata
Masanori
M
Ohba
Tetsuro
T
Ando
Takashi
T
Hatsushika
Kyosuke
K
Suenaga
Fumiko
F
Shimokawa
Naomi
N
Ohnuma
Yuko
Y
Katoh
Ryohei
R
Ogawa
Hideoki
H
Nakao
Atsuhito
A
D000111:Acetylcysteine / Q000494:pharmacology; D000281:Administration, Intranasal; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D045424:Complex Mixtures / Q000633:toxicity*; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000276:immunology; D012307:Risk Factors; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D000094632:Thymic Stromal Lymphopoietin
D045424:Complex Mixtures; D016207:Cytokines; D016166:Free Radical Scavengers; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014028:Tobacco Smoke Pollution; D000111:Acetylcysteine; D000094632:Thymic Stromal Lymphopoietin